Protection against toxicity of high dose chemotherapy in mice transfected with double-mutant dihydrofolate reductase-cytidine deaminase gene Journal Article

  


Authors: Lu, P.; Jin, F.; Chen, B.; Yao, F.; Wang, S. B.; Chen, J. Q.; Xu, H. M.; Zhao, S. C.
Article Title: Protection against toxicity of high dose chemotherapy in mice transfected with double-mutant dihydrofolate reductase-cytidine deaminase gene
Abstract: AIM: To explore the feasibility of transferring dihydrofolate reductase-(DHFR) gene and cytidine deaminase (CD) fusion gene into mouse bone marrow (BM) cells to induce resistance to high dose methotrexate (MTX) and cytosine arabinoside (Ara-C), and to improve the tolerance of myelosuppression following combination chemotherapy. METHODS: Human double-mutant DHFR-CD fusion gene was transferred into mouse BM cells by retroviral vector Granulocyte-macrophage colony-forming unit (CFU-GM) assay was performed for retrovirally infected and drug treated mouse BM cells. DNA was extracted from mouse BM, and the expression of drug resistant genes was examined by PCR. RESULTS: Drug resistant colonies were formed by donor mouse BM cells co-cultured with the retrovirus producing cells, as well as the BM cells from recipient mice transplanted with the fusion gene transfected BM cells (CFU-GM of donor mice was 14%, χ 2 = 42.55, P<0.01; CFU-GM of recipient mice was 20%, χ 2 = 44.26, P<0.01). The drug resistance to both MTX and Ara-C was also increased in the recipient mice. The survival rate of gene transferred mice was significantly higher compared with the control mice χ 2 = 7.42, P<0.01. Expression of the DHFR-CD fusion gene in the transfected mice was confirmed by PCR. CONCLUSION: Double drug resistant genes can be integrated and expressed in mouse bone marrow cells; furthermore, they can increase the drug resistance to MTX and Ara-C.
Keywords: controlled study; survival rate; nonhuman; chemotherapy; cytarabine; methotrexate; drug megadose; polymerase chain reaction; animal cell; mouse; bone marrow suppression; animal experiment; animal model; combination chemotherapy; gene transfer; gene expression regulation; statistical significance; dna; cytidine deaminase; genetic transfection; gene fusion; gene therapy; retrovirus vector; bone marrow cell; dihydrofolate reductase; dna determination; retrovirus; colony forming unit gm; genetic resistance
Journal Title: World Chinese Journal of Digestology
Volume: 13
Issue: 4
ISSN: 1009-3079
Publisher: WJC Press  
Date Published: 2005-02-15
Start Page: 464
End Page: 467
Language: Chinese
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-20444482806&partnerID=40&md5=ba71a0fcf71aadffc51708090272944f
Notes: --- - "Export Date: 24 October 2012" - "CODEN: SHXZF" - "Source: Scopus"